4CZC

Crystal structure of the siroheme decarboxylase NirDL in co-complex with iron-uroporphyrin III analogue

Summary for 4CZC

• Entry DOI: 10.2210/pdb4czc/pdb
• Descriptor: NIRD-LIKE PROTEIN, Fe(III) Uroporphyrin (3 entities in total)
• Functional Keywords: transcription, bifunctional enzyme, transcriptional regulator
• Biological source: HYDROGENOBACTER THERMOPHILUS
• Total number of polymer chains: 1
• Total formula weight: 41158.03

Authors

Schmelz, S.,Kriegler, T.M.,Haufschildt, K.,Layer, G.,Heinz, D.W. (deposition date: 2014-04-17, release date: 2014-07-30, Last modification date: 2024-10-23)

Primary citation

Haufschildt, K.,Schmelz, S.,Kriegler, T.M.,Neumann, A.,Streif, J.,Arai, H.,Heinz, D.W.,Layer, G.
The Crystal Structure of Siroheme Decarboxylase in Complex with Iron-Uroporphyrin III Reveals Two Essential Histidine Residues
J.Mol.Biol., 426:3272-, 2014

PubMed Abstract: The isobacteriochlorin heme d1 serves as an essential cofactor in the cytochrome cd1 nitrite reductase NirS that plays an important role for denitrification. During the biosynthesis of heme d1, the enzyme siroheme decarboxylase catalyzes the conversion of siroheme to 12,18-didecarboxysiroheme. This enzyme was discovered recently (Bali S, Lawrence AD, Lobo SA, Saraiva LM, Golding BT, Palmer DJ et al. Molecular hijacking of siroheme for the synthesis of heme and d1 heme. Proc Natl Acad Sci USA 2011;108:18260-5) and is only scarcely characterized. Here, we present the crystal structure of the siroheme decarboxylase from Hydrogenobacter thermophilus representing the first three-dimensional structure for this type of enzyme. The overall structure strikingly resembles those of transcriptional regulators of the Lrp/AsnC family. Moreover, the structure of the enzyme in complex with a substrate analog reveals first insights into its active-site architecture. Through site-directed mutagenesis and subsequent biochemical characterization of the enzyme variants, two conserved histidine residues within the active site are identified to be involved in substrate binding and catalysis. Based on our results, we propose a potential catalytic mechanism for the enzymatic reaction catalyzed by the siroheme decarboxylase.

PubMed: 25083922
DOI: 10.1016/J.JMB.2014.07.021

Experimental method

X-RAY DIFFRACTION (2.9 Å)